Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice
Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice
复制标题
龙胆苦苷通过下调小鼠杏仁核中的 GluN2B 受体来减轻利血平引起的疼痛/抑郁二联体
DOI：
10.1007/s12017-013-8280-8
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发表时间：
2014-06-01
影响因子：
3.5
通讯作者：
Zhao, Ming-gao
中科院分区：
文献类型：
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作者：
Liu, Shui-bing;Zhao, Rong;Zhao, Ming-gao
流行病学研究表明，疼痛经常与抑郁症同时发生。 Gentiopicroside (Gent) 是一种从黄龙胆中分离出来的环烯醚萜化合物，具有镇痛特性并抑制小鼠前扣带皮层中含有 GluN2B 的 N-甲基-d-天冬氨酸 (NMDA) 受体的表达。然而，Gent 对利血平引起的疼痛/抑郁二元组的影响及其潜在机制尚不清楚。利血平给药（每天 1 mg/kg 皮下注射，持续 3 天）导致伤害性阈值显着降低，这可以通过响应辐射热源和机械异常性疼痛的缩爪潜伏期缩短来证明。行为检测表明，强迫游泳测试中的不动时间显着增加，而开放场地测试中的中心区域时间和总移动距离则减少。此外，利血平治疗的动物表现出氧化应激增加。全身Gent给药可剂量依赖性地改善与利血平引起的疼痛/抑郁二元相关的行为缺陷。同时，注射利血平的小鼠杏仁核中生物胺水平（去甲肾上腺素、多巴胺和血清素）的降低与 caspase-3 水平和含 GluN2B 的 NMDA 受体的增加相结合。 Gent 显着逆转了杏仁核中生物胺、caspase-3 和含有 GluN2B 的 NMDA 受体水平的变化。然而，Gent 并不影响含有 GluN2A 的 NMDA 受体的表达。同时使用 GluN2B 受体拮抗剂 Ro25-6981 可以阻断 Gent 对氧化应激的抑制作用。我们的研究提供了强有力的证据，证明 Gent 通过下调杏仁核中的 GluN2B 受体来抑制利血平引起的疼痛/抑郁二元体。
Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated fromGentiana luteathat exhibits analgesic properties and inhibits the expression of GluN2B-containingN-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.